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PubMed:16551362 JSONTXT

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2015-BEL-Sample-2

Id Subject Object Predicate Lexical cue
BEL:20039054 1913-2048 kin(p(MGI:Pdpk1)) increases p(MGI:Mmp14) denotes PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collage
BEL:20032024 1913-2048 cat(p(MGI:Mmp14)) increases cat(p(MGI:Mmp2)) denotes PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collage

PubmedHPO

Id Subject Object Predicate Lexical cue
T1 186-199 HP_0003002 denotes breast cancer
T2 186-199 HP_0100013 denotes breast cancer
T3 193-199 HP_0002664 denotes cancer
T4 205-210 HP_0002664 denotes tumor

PubMed_Structured_Abstracts

Id Subject Object Predicate Lexical cue
T1 128-776 BACKGROUND denotes Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile.
T2 786-1092 METHODS denotes Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC.
T3 1102-1758 RESULTS denotes Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples.
T4 1771-2186 CONCLUSIONS denotes These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its importance in the metastatic process.